rs2887531

Positions:

• chr12-946721-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_134424.4(RAD52):​c.-19+2881A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 152,086 control chromosomes in the GnomAD database, including 5,351 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.26 (5351 hom., cov: 33)
• Consequence: RAD52 NM_134424.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.533

Genes affected

RAD52 (HGNC:9824): (RAD52 homolog, DNA repair protein) The protein encoded by this gene shares similarity with Saccharomyces cerevisiae Rad52, a protein important for DNA double-strand break repair and homologous recombination. This gene product was shown to bind single-stranded DNA ends, and mediate the DNA-DNA interaction necessary for the annealing of complementary DNA strands. It was also found to interact with DNA recombination protein RAD51, which suggested its role in RAD51 related DNA recombination and repair. A pseudogene of this gene is present on chromosome 2. Alternative splicing results in multiple transcript variants. Additional alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known. [provided by RefSeq, Jul 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAD52	NM_134424.4	c.-19+2881A>G		intron_variant		ENST00000358495.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAD52	ENST00000358495.8	c.-19+2881A>G		intron_variant		1	NM_134424.4	P2

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39660 AN: 151968 Hom.: 5345 Cov.: 33

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.260

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.261 AC: 39694 AN: 152086 Hom.: 5351 Cov.: 33 AF XY: 0.260 AC XY: 19358 AN XY: 74360

Gnomad4 AFR AF: 0.299

Gnomad4 AMR AF: 0.287

Gnomad4 ASJ AF: 0.253

Gnomad4 EAS AF: 0.364

Gnomad4 SAS AF: 0.148

Gnomad4 FIN AF: 0.233

Gnomad4 NFE AF: 0.236

Gnomad4 OTH AF: 0.260

Alfa AF: 0.245 Hom.: 567

Bravo AF: 0.270

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.72
DANN	Benign	0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2887531; hg19: chr12-1055887;